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Spatial Proteomics Identifies JAKi as Treatment for a Lethal Skin Disease

Toxic epidermal necrolysis (TEN) is a severe, life-threatening skin reaction caused by certain medications where the immune system mediates keratinocyte cell death, causing severe blistering and skin peeling over ~30% of the body. It’s fatal in one out of three cases. I was in awe when I realized that spatial proteomic techniques like Deep Visual Proteomics allow scientists to analyze archived samples, such as those that have been formalin-fixed and paraffin-embedded! It’s like opening cold cases and being able to retrieve more information. I also loved seeing how they used DermaCult™ in the research!

Precision Enhancement of CAR-NK Cells Through Non-Viral Engineering and Highly Multiplexed Base Editing

CRISPR-Cas9-based gene editing has come such a long way! I am particularly fascinated by base editors because they offer a more precise, efficient, and safer way to modify DNA as they don’t cause double-stranded breaks. The authors of this preprint combined base editors targeting different genes to simultaneously achieve loss-of-function and gain-of-function mutations in NK cells. NK cells, known for their ability to kill transformed cells, have shown only moderate responses in clinical trials, necessitating advanced genome engineering. The researchers generated IL-15 armored CD19 CAR-NK cells with improved functionality against Burkitt’s lymphoma.

Achieving Optical Transparency in Live Animals with Absorbing Molecules

Imaging live animals has been a challenge researchers have been trying to overcome for many, many decades! This work is a big step toward finally making it more feasible. It has also made me wonder if eating Doritos would make my kids’ skin more transparent, so I have been keeping a close eye on them when they indulge!

By applying a solution of tartrazine—a common food color used to give Doritos their orange color—to live mice, researchers reversibly made skin, muscle, and connective tissues transparent. Conventional wisdom would suggest that strongly absorbing molecules would reduce transparency, but this work shows that specific dye molecules can increase the refractive index of an aqueous medium, reducing the refractive index contrast between water and lipids, and thereby achieving optical transparency.

A Flexible High-Precision Photoacoustic Retinal Prosthesis

We’ve all heard about the augmented-reality glasses that tech companies are releasing to enhance the information we see, but is there any way we could use that concept to develop more advanced devices to treat patients with vision disorders? An implantable photoacoustic retinal prosthetic device that uses light and sound to restore vision sounds like complete science fiction! This technology allows for more precise stimulation to improve spatial resolution and has the ability to restore a larger visual field, which has been a limitation of previously developed devices.

Induced Pluripotent Stem Cell-Derived Corneal Epithelium for Transplant Surgery: a Single-Arm, Open-Label, First-in-Human Interventional Study in Japan

As a scientist working in ophthalmology and vision research, it is absolutely amazing to see the progress the field is making on the use of iPSC-derived ocular cells to treat various ocular diseases. This study makes some conclusions parallel to those from the clinical data reported for retinal pigment epithelial cell transplant, such as efficacy being possible without HLA-matching and short-term immunosuppression being required to improve graft survival. The future looks promising and I’m excited to see where the field is headed!

Brain Chimeroids Reveal Individual Susceptibility to Neurotoxic Triggers

Brain organoids make excellent models for researching early stages of human neurodevelopment; however, scalability is a limiting factor. I found this publication interesting because it presents a method to address this limitation by representing multiple individuals in a single organoid. Watching the brain organoid field grow has been exciting; it seems that every year there is a new way to generate or assemble organoids to better model the brain in vitro!

Glioblastoma-Cortical Organoids Recapitulate Cell State Heterogeneity and Intercellular Transfer

I found this article interesting because the authors showed that the oligodendrocyte progenitor cell (OPC)-like cellular state is maintained, which is noteworthy compared to traditional tumorsphere cultures. It also demonstrated potential microenvironment remodeling by malignant cells in organoids which is very cool. Glioblastoma is a devastating brain tumor characterized by inter- and intra-tumoral heterogeneity. This heterogeneity is better represented in vitro through organoid models. Glioblastoma-brain organoid co-cultures (termed GLICOs) were and the amount of research using this method is increasing every year.

The Emergence of Sox and POU Transcription Factors Predates the Origins of Animal Stem Cells

Sox and POU are transcription factors of pluripotency and stemness, once believed to be uniquely specific to animals. The authors investigated the evolutionary origins of these key regulators by examining unicellular relatives of animals—choanoflagellates and filastereans—and found orthologs to Sox and POU transcription factors. This is a fascinating study! The identification of Sox- and POU-related factors in our unicellular relatives is important in our understanding of how multicellular organisms and stem cells arose through evolution.